Journal
EUROPEAN JOURNAL OF PHARMACOLOGY
Volume 403, Issue 1-2, Pages 37-44Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/S0014-2999(00)00578-1
Keywords
opioid receptor; ligand selectivity; mutagenesis; [S-35]GTP gamma S
Categories
Funding
- NIDA NIH HHS [R01-DA02265, R01-DA08920] Funding Source: Medline
Ask authors/readers for more resources
We hypothesized that the selectivity profile of the rat mu-opioid receptor for opioid receptor-selective ligands is determined by the nature of the amino acid residues at highly divergent sites in the ligand-binding pocket. To determine which characteristics of these residues contribute to opioid receptor ligand selectivity, we made various mutant receptors that replaced the Lys(303) and Trp(315) residues near the extracellular interface of transmembrane domains VI and VII, respectively. Ligand binding determinations using transiently transfected monkey kidney epithelial (COS-1) cells show that Lys(303) mutations cause little change in the receptor binding profile, whereas the Trp(318) mutant receptors have considerably lower affinity for mu-opioid receptor-selective ligands and greatly increased affinity for delta-opioid receptor-selective ligands. The nature of these mutations show that this effect is not due to sterics or charge alone. [S-35]guanosine-5'-O-(3-thio)-triphosphate ([S-35]GTP gamma S) activity assays show that these residues may influence functional, as well as binding selection. We conclude that a primary role for Trp(318) is to form a basis for ligand selectivity. (C) 2000 Elsevier Science B.V. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available